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MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D) (Meld-ATG)

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ClinicalTrials.gov Identifier: NCT04509791
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Tracking Information
First Submitted Date  ICMJE August 7, 2020
First Posted Date  ICMJE August 12, 2020
Last Update Posted Date September 16, 2021
Actual Study Start Date  ICMJE November 24, 2020
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
the area under the stimulated C-peptide response curve [ Time Frame: over the first 2 hours of a mixed meal tolerance test (MMTT) at 12 months post treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2020)
the area under the stimulated C-peptide response curve [ Time Frame: over the first 2 hours of a MMTT [ mixed meal tolerance test] at 12 months post treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
  • the area under the stimulated C-peptide response curve [ Time Frame: over the first 2 hours of a MMTT at baseline, 3, 6 and 12 months ]
  • dry blood spot (DBS) C-peptide measurements [ Time Frame: at all observation times ]
  • Cluster of differentiation 4 (CD4) positive T cells and Cluster of differentiation 8 (CD8) positive T cells [ Time Frame: over 12 months ]
  • HbA1c [ Time Frame: over 12 months ]
  • insulin requirements [ Time Frame: over 12 months ]
    The need for insulin (units) on a daily basis
  • T1D-associated autoantibodies (glutamic acid decarboxylase antibodies (GADA), insulin auto-antibodies (IAA), IA-2 antibodies (IA-2A) and Zinc transporter 8 antibodies (ZnT8A)) [ Time Frame: over 12 months ]
    The presence of T1D-associated autoantibodies
  • continuous glucose monitoring (CGM) measurements ( time in range, time above time below) [ Time Frame: over 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2020)
  • the area under the stimulated C-peptide response curve [ Time Frame: over teh first 2 hours of a MMTT at baseline, 3, 6 and 12 months ]
  • DBS [dry blood spot] C-peptide measurements [ Time Frame: at all observation times ]
  • CD4 positive T cells and CD8 positive T cells [ Time Frame: over 12 months ]
  • HbA1c [ Time Frame: over 12 months ]
  • insulin require months [ Time Frame: over 12 months ]
  • T1D-associated autoantibodies ( GADA [glutamic acid decarboxylase antibodies], IAA [insulin auto-antibodies], IA-2A [IA-2 antibodies] and ZnT8A [ Time Frame: over 12 months ]
  • CGM [continuous glucose monitoring] measurements ( time in range, time above time below) [ Time Frame: over 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D)
Official Title  ICMJE MELD-ATG: Phase II, Dose Ranging, Efficacy Study of Anti-thymocyte Globulin (ATG) Within 6 Weeks of Diagnosis of Type 1 Diabetes (T1D)
Brief Summary

A phase II, Multi-centre, randomised, double-blind, placebo-controlled, Multi-arm parallel cohort trial.

  • to investigate the effect of 2.5 mg/kg og ATG on the preservation of stimulated C-peptide at 12 months compared to placebo
  • to identify the minimally effective dose of ATG that shows an effect on C-peptide when compared to placebo at 12 months
Detailed Description

A phase II, Multi-centre, randomised, double-blind, placebo-controlled, Multi-arm parallel cohort trial.

Randomisation wil be stratified by age. The trial consist of seven cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg.

ATG total dose in a 1:1:1:1 allocation ratio. There will be an initial age step down selection of this cohort with recruitment starting with dose aged 12-25 years and, providing no new safety concerns are raised in the first 10 participants to receive active dose, progressing to all ages (5-25 years) The next two cohorts of 12 participants will be randomised to placebo, 2.5 mg/kg, and 2 specified middle ATG total doses in a 1:1:1:1 allocation ratio.

The next four cohorts of 15 participants will be randomised to placebo, 2.5 mg/kg, and a single selected middle ATG total doses in a 1:1:1 allocation ratio.

This design allows sequential adjustment of the middle doses to be explored following review of all safety and early efficacy data by the Independent Data Monitoring Committee ( IDMC) and Dose Determine Committee (DDC) to seek the minimum effective dose

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
the trial design consists of 7 cohorts, each recruited sequentially, with between 3 and 5 treatment arms ( there will be fewer arms for later cohorts)
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
MELD - ATG : Minimum effective low dose ant-human thymocyte globulin (rabbit)
Other Name: ATG
Study Arms  ICMJE
  • Placebo Comparator: placebo
    placebo arm
    Intervention: Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
  • Active Comparator: 2.5 mg ATG/kg
    the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
    Intervention: Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
  • Active Comparator: 1.5 mg ATG/kg
    the next two cohorts of 12 participants will be randomised to placebo, 2.5 mg/Kg, and 2 specified middle ATG total doses in a 1:1:1:1 allocation ratio
    Intervention: Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
  • Active Comparator: 0.5 mg ATG/kg
    The next four cohorts of 15 participants will be randomised to placebo, 2.5 mg/kg and a single selected middle ATG total dose in a 1:1:1 allocation ratio
    Intervention: Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
  • Active Comparator: 0.1 mg ATG/kg
    the trial consists of 7 cohorts. The first cohort of 30 participants will be randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg en 0.1 mg/kg in a 1:1:1:1:1 allocation ratio
    Intervention: Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 10, 2020)
114
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • has given written informed consent to participate; or have a parent or legal guardian provide written informed consent. Individual under the age of consent will be asked to assent to trial participation
  • be aged > 5 years to < 25 years at written informed consent/assent
  • have been diagnosed with T1d within 3-9 weeks of planned treatment day 1
  • have random C-peptide levels > 200 pmol/L measured at screening, as tested centrally
  • have 1 or more diabetes-related autoantibody (GADA, IA-2A or ZnT8A) present at screening, as tested centrally
  • will be > 6 weeks form last live immunisation at planned treatment day 1 and be willing to forgo live vaccines during the trial until 6 months post treatment
  • be willing to comply with intensive diabetes management

Exclusion Criteria:

  • Type 2 diabetes
  • Evidence of prior or current tuberculosis (TB) infection
  • Clinically significant abnormal full blood count (FBC), renal function or liver function at screening
  • Requiring use of other immunosuppressive or immunomodulation agents, including chronic use of systemic steroids
  • any active chronic infections at screening, or any active acute or chronic infections at baseline or on treatment day, which would contraindicate any additional immunosuppression
  • seropositive for human immunodeficiency virus (HIV),hepatitis B of hepatitis C infection at screening
  • positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) based on local testing regimen
  • unwilling to use appropriate contraception if sexually active during the trial, from date of written informed consent until completion of the 12-month follow-up visit
  • any history of malignancies, other than skin
  • current or ongoing use of non-insulin pharmaceuticals that effect glycaemic control
  • active participation in another T1D treatment interventional trial in the previous 30 days prior to screening ( excluding treatment with insulin)
  • any prior treatment with ATG, Abatacept or Anti-CD3 monoclonal antibody (Anti-CD3)
  • known allergy to ATG or to similar products
  • any condition, complicating medical issues, or abnormal clinical laboratory results that the investigator judges may adversely affect trial conduct, cause increased risk to the participant, or compromise the trial results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chantal Mathieu, MD,pHD +3216346994 chantal.mathieu@uzleuven.be
Contact: Lisa Van Ryckeghem, pHD +3216342129 MELD-ATG@uzleuven.be
Listed Location Countries  ICMJE Austria,   Belgium,   Denmark,   Finland,   Germany,   Italy,   Poland,   Slovenia,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04509791
Other Study ID Numbers  ICMJE S63466
2019-003265-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Universitaire Ziekenhuizen Leuven
Study Sponsor  ICMJE Universitaire Ziekenhuizen Leuven
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: chantal Mathieu, MD,pHD Universitaire Ziekenhuizen Leuven
PRS Account Universitaire Ziekenhuizen Leuven
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP